ABSTRACT
The aim of this research was to follow parallelly the clinical status of a patient and the dynamics of the serotonin transporter (SERT), a likely player in the effect of electroconvulsive treatment (ECT), a powerful tool against deep depression. A patient affected by major depression with catatonic features, not responding to pharmacological therapy, underwent ECT. Evaluations of the binding of labelled paroxetine to venous blood platelet SERT were parallel to the assessments of clinical improvements. The density of platelet SERT, starting from a low level before ECT, displayed an initial steep increase peaking the day after the third electroconvulsive session (5 days after the start of ECT). This was followed by a rapid decrease, which seemed to precede the process of clinical recovery. These results were found in a case of unavoidable ECT treatment. If generalizable, they suggest interesting ideas about the still mysterious mechanism of ECT antidepressant action.
Subject(s)
Blood Platelets/metabolism , Catatonia/therapy , Electroconvulsive Therapy/methods , Serotonin Plasma Membrane Transport Proteins/blood , Aged , Catatonia/blood , Catatonia/complications , Clomipramine/therapeutic use , Depressive Disorder, Major/blood , Depressive Disorder, Major/complications , Depressive Disorder, Major/therapy , Dose-Response Relationship, Drug , Female , Humans , Psychiatric Status Rating Scales , Selective Serotonin Reuptake Inhibitors/metabolism , Selective Serotonin Reuptake Inhibitors/therapeutic use , Time FactorsABSTRACT
The density of the serotonin transporter in the plasma membranes of blood platelets was evaluated by labelled paroxetine binding in three different groups. These groups were: normal controls, epileptic patients having undergone a recent seizure (less than 4 days before) and patients who equally recently presented psychogenic non-epileptic seizures (pseudoseizures). Real seizures resulted in a significant decrease of membrane serotonin transporter density. In the instances of pseudoseizures, its membrane density was undistinguishable from that of normal controls. These data lend further support to the idea that down regulation of serotonin transporter may play a homeostatic role in the cessation of epileptic seizures.
Subject(s)
Blood Platelets/metabolism , Epilepsy/blood , Serotonin Plasma Membrane Transport Proteins/blood , Adolescent , Adult , Aged , Anticonvulsants/therapeutic use , Cell Membrane/metabolism , Epilepsy/drug therapy , Female , Humans , Male , Middle Aged , Paroxetine/metabolism , TritiumABSTRACT
The binding of labelled paroxetine to the serotonin transporter (SERT) of platelet membranes has been studied in both venous and mixed venous/arterial blood of the rat. In addition, we studied the inhibition of paroxetine binding to SERT by quipazine and N-methyl-quipazine (NMQ). The results indicate differences in affinity for the two test drugs, quipazine and NMQ, in venous vs. mixed venous/arterial blood. This suggests different post-translational modifications of SERT in platelets of arterial vs. venous blood.
Subject(s)
Arteries/metabolism , Blood/metabolism , Serotonin Plasma Membrane Transport Proteins/blood , Veins/metabolism , Animals , Blood Platelets/metabolism , Female , Humans , Male , Paroxetine/metabolism , Protein Processing, Post-Translational , Quipazine/analogs & derivatives , Quipazine/metabolism , Rats , Rats, Wistar , Serotonin Plasma Membrane Transport Proteins/genetics , Serotonin Receptor Agonists/chemistry , Serotonin Receptor Agonists/metabolism , Selective Serotonin Reuptake Inhibitors/metabolismABSTRACT
Serotonin transporter (SERT) was studied by [3H]-paroxetine binding in blood platelets from controls and epileptic patients with generalized convulsive seizures. The average KD and BMax were not different in the two cases. However, a significant decrease was found in the serotonin transporter density in the platelet membranes from patients having undergone an epileptic seizure less than 4 days before. This circumstance may indicate a homeostatic reaction to the epileptic attack.
Subject(s)
Blood Platelets/metabolism , Epilepsy, Tonic-Clonic/metabolism , Membrane Glycoproteins/blood , Membrane Transport Proteins/blood , Nerve Tissue Proteins/blood , Seizures/metabolism , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Paroxetine/blood , Paroxetine/pharmacokinetics , Serotonin/blood , Serotonin Plasma Membrane Transport Proteins , Selective Serotonin Reuptake Inhibitors/blood , Selective Serotonin Reuptake Inhibitors/pharmacokineticsABSTRACT
3-Quinolinecarboxamides have been synthesized and evaluated for their binding to the human NK(1) receptor. Several secondary amide derivatives show NK(1) receptor affinity in the picomolar range. The most active compound, hydroxymethylcarboxamide 3h showing an IC(50) value in the subpicomolar range, behaved as an agonist of NK(1) receptor in endothelial cell proliferation, inositol phosphate turnover, and NO-mediated cyclic GMP accumulation, thus proving it to be the first non-peptide NK(1) receptor agonist showing very high potency.
